P930: ELRANATAMAB MONOTHERAPY OR IN COMBINATION WITH DARATUMUMAB VS DARATUMUMAB + POMALIDOMIDE + DEXAMETHASONE FOR PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: PHASE 3 MAGNETISMM-5 STUDY, PART 2
Authors: Xavier Leleu, Shinsuke Iida, C. Ola Landgren, Alexander Lesokhin, Eric Leip, Arthur Kudla, Gregory Finn, Lugui Qiu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Elranatamab is a humanized bispecific antibody targeting B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells. Data from the phase 1 MagnetisMM-1 study demonstrated promising efficacy and manageable safety of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM). Data from the phase 2 MagnetisMM-3 study also demonstrated that elranatamab was efficacious and well tolerated at the recommended phase 2 dose (76 mg once weekly on a 28-d cycle with a step-up priming dose regimen during the first week of treatment) in patients with RRMM. The combination of elranatamab with daratumumab (ED), a CD38-directed therapy, is supported by daratumumab’s proposed dual mechanisms of action contributing to antitumor response and increased efficacy of elranatamab. Aims: The aim of the MagnetisMM-5 study is to evaluate the efficacy and safety of elranatamab monotherapy and ED in patients with RRMM. Data from Part 1 of MagnetisMM-5, the safety lead-in cohort, showed that ED is efficacious, well tolerated, and can be safely administered in combination at the recommended single-agent dose (Grosicki et al, Blood, 2022). Methods: MagnetisMM-5 (NCT05020236) is an ongoing, open-label, multicenter, randomized phase 3 study enrolling ~555 patients in Part 2. Patients are randomized 1:1:1 to receive subcutaneous elranatamab, or ED, or daratumumab + pomalidomide + dexamethasone (DPd). Daratumumab is administered subcutaneously. Patients are stratified by prior lines of therapy (1 vs 2–3) and prior treatment with CD38-directed therapy (yes vs no). The primary endpoint is progression-free survival (PFS) by blinded independent review per International Myeloma Working Group (IMWG) response criteria. Secondary endpoints include overall survival, PFS on next-line treatment per IMWG response criteria, objective response rate, duration of response, complete response (CR) rate, duration of CR, time to response, overall and sustained minimal residual disease negativity rates, safety, quality of life, immunogenicity, and pharmacokinetics. Key inclusion criteria are age ≥18 y, MM diagnosis with measurable disease according to IMWG criteria, and ECOG performance status 0–2. Patients should have received prior anti-myeloma therapy, including treatment with lenalidomide and a proteasome inhibitor. Key exclusion criteria include smoldering MM, plasma cell leukemia, amyloidosis, POEMS syndrome, stem cell transplant within 12 wk of enrollment or active graft versus host disease, active, uncontrolled bacterial, fungal, or viral infections, previous treatment with BCMA-directed therapy, and CD38-directed therapy within 6 mo of the first dose of study treatment. MagnestisMM-5 is recruiting from centers in 23 countries. Results: N/A Summary/Conclusion: N/A Keywords: Multiple myeloma, Clinical trial, B-cell maturation antigen, Bispecific